Controlled release (CR) formulations are useful in situations where drug release over an extended period of time is required, such as repetitive, intermittent dosings of a drug from one or more immediate release systems. Controlled release drug delivery systems are used to improve the therapeutic response by providing blood levels that are more consistent and stable compared to immediate release dosage forms. Existing CR dosage forms are based on matrix tablets or coated tablets or capsules filled with coated drug particles or granules. These systems, however, have several drawbacks, including the lack of content uniformity and homogeneity, particularly with compounds present in low dosages. Moreover, low dose compounds, as well as compounds which are moisture sensitive, can be difficult to handle in powder form, which is the form typically used to prepare tablets or powder-filled hard gelatin capsules.
Controlled release formulations, particularly of drugs such as opioid analgesics which are prone to abuse, can be susceptible to misuse. Currently available sustained release formulations of such drugs, which contain a relatively large amount of drug meant to be released from the formulation over an extended time period, are particularly attractive to abusers since the sustained release action can be destroyed by crushing or grinding the formulation. The resulting material (i.e., the crushed formulation) can no longer control the release of drug. Depending on the drug, abusers can then (1) snort the material, (2) swallow the material or (3) dissolve the material in water and subsequently inject it intravenously. The dose of drug contained in the formulation is thus absorbed immediately through the nasal or GI mucosa (for snorting or swallowing, respectively) or is administered in a bolus to the systemic circulation (for IV injection). These abuse methods result in the rapid bioavailability of relatively high doses of drug, giving the abuser a “high”. Since relatively simple methods (crushing, grinding, chewing and/or dissolution in water) can be used to transform such formulations into an abusable form, they provide virtually no deterrent to a potential abuser.
There is a need for a liquid controlled-release formulation is which low dose compounds can be more easily formulated.
There also is a need for a controlled release formulation which can minimize or prevent the misuse of drugs which are prone to abuse by making it more difficult for the drug to be extracted from the dosage form.
Therefore, it is an object of the invention to provide a dual controlled release liquid matrix for the formulation of low dose drugs, and methods of manufacture thereof.
It is further an object of the invention to provide a dual controlled release liquid matrix which can minimize or prevent the misuse of drugs which are prone to abuse.